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First published online 25 April 2006
doi: 10.1242/jcs.02935


Journal of Cell Science 119, 2145-2155 (2006)
Published by The Company of Biologists 2006
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Research Article

The junctional SR protein JP-45 affects the functional expression of the voltage-dependent Ca2+ channel Cav1.1

Ayuk A. Anderson1, Xavier Altafaj2, Zhenlin Zheng3, Zhong-Min Wang3, Osvaldo Delbono3,4, Michel Ronjat2, Susan Treves1 and Francesco Zorzato5,*

1 Departments of Anaesthesia and Research, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland
2 INSERM U607/CEA/UJF, Lab CCFP/DRDC, Rue des Martyrs 17, 38054, Grenoble, Cedex 9 France
3 Department of Physiology and Pharmacology, Gerontology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
4 Department of Internal Medicine, Gerontology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
5 Department of Experimental and Diagnostic Medicine, General Pathology Section, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy

* Author for correspondence (e-mail: zor{at}unife.it)

Accepted 14 February 2006

JP-45, an integral protein of the junctional face membrane of the skeletal muscle sarcoplasmic reticulum (SR), colocalizes with its Ca2+-release channel (the ryanodine receptor), and interacts with calsequestrin and the skeletal-muscle dihydropyridine receptor Cav1. We have identified the domains of JP-45 and the Cav1.1 involved in this interaction, and investigated the functional effect of JP-45. The cytoplasmic domain of JP-45, comprising residues 1-80, interacts with Cav1.1. JP-45 interacts with two distinct and functionally relevant domains of Cav1.1, the I-II loop and the C-terminal region. Interaction between JP-45 and the I-II loop occurs through the {alpha}-interacting domain in the I-II loop. ß1a, a Cav1 subunit, also interacts with the cytosolic domain of JP-45, and its presence drastically reduces the interaction between JP-45 and the I-II loop. The functional effect of JP-45 on Cav1.1 activity was assessed by investigating charge movement in differentiated C2C12 myotubes after overexpression or depletion of JP-45. Overexpression of JP-45 decreased peak charge-movement and shifted VQ1/2 to a more negative potential (-10 mV). JP-45 depletion decreased both the content of Cav1.1 and peak charge-movements. Our data demonstrate that JP-45 is an important protein for functional expression of voltage-dependent Ca2+ channels.

Key words: Voltage-dependent Ca2+ channel, JP-45, Sarcoplasmic reticulum, Excitation-contraction coupling




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Proc. Natl. Acad. Sci. USAHome page
O. Delbono, J. Xia, S. Treves, Z.-M. Wang, R. Jimenez-Moreno, A. M. Payne, M. L. Messi, A. Briguet, F. Schaerer, M. Nishi, et al.
Loss of skeletal muscle strength by ablation of the sarcoplasmic reticulum protein JP45
PNAS, December 11, 2007; 104(50): 20108 - 20113.
[Abstract] [Full Text] [PDF]




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